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121.
Singh KhD Kirubakaran P Nagarajan S Sakkiah S Muthusamy K Velmurgan D Jeyakanthan J 《Journal of molecular modeling》2012,18(1):39-51
To date, no suitable vaccine or specific antiviral drug is available to treat Chikungunya viral (CHIKV) fever. Hence, it is
essential to identify drug candidates that could potentially impede CHIKV infection. Here, we present the development of a
homology model of nsP2 protein based on the crystal structure of the nsP2 protein of Venezuelan equine encephalitis virus
(VEEV). The protein modeled was optimized using molecular dynamics simulation; the junction peptides of a nonstructural protein
complex were then docked in order to investigate the possible protein–protein interactions between nsP2 and the proteins cleaved
by nsP2. The modeling studies conducted shed light on the binding modes, and the critical interactions with the peptides provide
insight into the chemical features needed to inhibit the CHIK virus infection. Energy-optimized pharmacophore mapping was
performed using the junction peptides. Based on the results, we propose the pharmacophore features that must be present in
an inhibitor of nsP2 protease. The resulting pharmacophore model contained an aromatic ring, a hydrophobic and three hydrogen-bond
donor sites. Using these pharmacophore features, we screened a large public library of compounds (Asinex, Maybridge, TOSLab,
Binding Database) to find a potential ligand that could inhibit the nsP2 protein. The compounds that yielded a fitness score
of more than 1.0 were further subjected to Glide HTVS and Glide XP. Here, we report the best four compounds based on their
docking scores; these compounds have IDs of 27943, 21362, ASN 01107557 and ASN 01541696. We propose that these compounds could
bind to the active site of nsP2 protease and inhibit this enzyme. Furthermore, the backbone structural scaffolds of these
four lead compounds could serve as building blocks when designing drug-like molecules for the treatment of Chikungunya viral
fever. 相似文献
122.
Cho JH Rathnasingh C Song H Chung BW Lee HJ Seung D 《Bioprocess and biosystems engineering》2012,35(7):1081-1088
Klebsiella is one of the genera that has shown unbeatable production performance of 2,3-butanediol (2,3-BD), when compared to other microorganisms. In this study, two Klebsiella strains, K. pneumoniae (DSM 2026) and K. oxytoca (ATCC 43863), were selected and evaluated for 2,3-BD production by batch and fed-batch fermentations using glucose as a carbon source. Those strains' morphologies, particularly their capsular structures, were analyzed by scanning electron microscopy (SEM). The maximum titers of 2,3-BD by K. pneumoniae and K. oxytoca during 10 h batch fermentation were 17.6 and 10.9 g L(-1), respectively; in fed-batch cultivation, the strains showed the maximum titers of 50.9 and 34.1 g L(-1), respectively. Although K. pneumoniae showed higher productivity, SEM showed that it secreted large amounts of capsular polysaccharide, increasing pathogenicity and hindering the separation of cells from the fermentation broth during downstream processing. 相似文献
123.
Kapoor D Kumar V Chandrayan SK Ahmed S Sharma S Datt M Singh B Karthikeyan S Guptasarma P 《Biochimica et biophysica acta》2008,1784(11):1771-1776
Using several tens of rationally-selected substitutions, insertions and deletions of predominantly non-contiguous residues, we have remodeled the solvent-exposed face of a beta sheet functioning as the substrate-binding and catalytically-active groove of a thermophile cellulase (Rhodothermus marinus Cel12A) to cause it to resemble, both in its structure and function, the equivalent groove of a mesophile homolog (Trichoderma reesei Cel12A). The engineered protein, a mesoactive-thermostable cellulase (MT Cel12A) displays the temperature of optimal function of its mesophile ancestor and the temperature of melting of its thermophile ancestor, suggesting that such 'grafting' of a mesophile-derived surface onto a thermophile-derived structural scaffold can potentially help generate novel enzymes that recombine structural and functional features of homologous proteins sourced from different domains of life. 相似文献
124.
Saxena R Kanudia P Datt M Dar HH Karthikeyan S Singh B Chakraborti PK 《The Journal of biological chemistry》2008,283(35):23754-23764
Genes encoding the peptide deformylase enzyme (def) are present in all eubacteria and are involved in the deformylation of the N-formyl group of newly synthesized polypeptides during protein synthesis. We compared the amino acid sequences of this enzyme in different mycobacterial species and found that they are highly conserved (76% homology with 62% identity); however, when this comparison was extended to other eubacterial homologs, it emerged that the mycobacterial proteins have an insertion region containing three consecutive arginine residues (residues 77-79 in Mycobacterium tuberculosis peptide deformylase (mPDF)). Here, we demonstrate that these three arginines are important for the activity of mPDF. Circular dichroism studies of wild-type mPDF and of mPDF containing individual conservative substitutions (R77K, R78K, or R79K) or combined substitutions incorporated into a triple mutant (R77K/R78K/R79K) indicate that such mutations cause mPDF to undergo structural alterations. Molecular modeling of mPDF suggests that the three arginines are distal to the active site. Molecular dynamics simulations of wild-type and mutant mPDF structures indicate that the arginines may be involved in the stabilization of substrate binding pocket residues for their proper interaction with peptide(s). Treatment with 5'-phosphothiorate-modified antisense oligodeoxyribonucleotides directed against different regions of def from M. tuberculosis inhibits growth of Mycobacterium smegmatis in culture. Taken together, these results hold out the possibility of future design of novel mycobacteria-specific PDF inhibitors. 相似文献
125.
126.
Phosphate Acquisition 总被引:25,自引:0,他引:25
127.
Sharma P Kumar J Garg G Kumar A Patowary A Karthikeyan G Ramakrishnan L Brahmachari V Sengupta S 《DNA and cell biology》2008,27(7):357-365
Epigenetic modifications, especially alteration in DNA methylation, are increasingly being recognized as a key factor in the pathogenesis of complex disorders, including atherosclerosis. However, there are limited data on the epigenetic changes in the coronary artery disease (CAD) patients. In the present study we evaluated the methylation status of genomic DNA from peripheral lymphocytes in a cohort of 287 individuals: 137 angiographically confirmed CAD patients and 150 controls. The differential susceptibility of genomic DNA to methylation-sensitive restriction enzymes was utilized to assess the methylation status of the genome. We observed that the genomic DNA methylation in CAD patients is significantly higher than in controls (p < 0.05). Since elevated homocysteine levels are known to be an independent risk factor for CAD and a key modulator of macromolecular methylation, we investigated the probable correlation between plasma homocysteine levels and global DNA methylation. We observed a significant positive correlation of global DNA methylation with plasma homocysteine levels in CAD patients (p = 0.001). Further, within a higher range of serum homocysteine levels (>/=12-50 muM), global DNA methylation was significantly higher in CAD patients than in controls. The alteration in genomic DNA methylation associated with cardiovascular disease per se appears to be further accentuated by higher homocysteine levels. 相似文献
128.
R. Karthikeyan Lawrence C. Davis Larry E. Erickson Kassim Al-Khatib Peter A. Kulakow Philip L. Barnes 《植物科学评论》2004,23(1):91-101
Appropriate environmental management of pesticides includes their proper application, use of filter strips and riparian buffers to contain pesticides in runoff from fields, prompt cleanup of spills, and treatment processes for wastewater associated with manufacturing and equipment usage. Plants have beneficial effects in the management of pesticide-contaminated soil and water, including direct metabolism of many pesticides, stimulation of microbial activity in the root zone, extraction of contaminated water, and reduction of infiltrating contaminated water. In this work, we review the literature on nontarget plants that can grow in pesticide-contaminated soil and water, and the fate of pesticides in filter strips, riparian buffers, and vegetated remediation environments. Past research indicates that there are significant differences in the tolerance of plants to pesticides present in soil and water, and that some plants are more effective than others in the remediation of pesticide-contaminated soil and water. Thus, there is value in the identification of tolerant plants and favorable plant-based remediation technologies for management of pesticides and contaminated sites. 相似文献
129.
Algorithms for theoretical reverse translation have direct applications in degenerate PCR. The conventional practice is to create several degenerate primers each of which variably encode the peptide region of interest. In the current work, for each codon we have analyzed the flanking residues in proteins and determined their influence on codon choice. From this, we created a method for theoretical reverse translation that includes information from flanking residues of the protein in question. Our method, named the neighbor correlation method (NCM) and its enhancement, the consensus-NCM (c-NCM) performed significantly better than the conventional codon-usage statistic method (CSM). Using the methods NCM and c-NCM, we were able to increase the average sequence identity from 77% up to 81%. Furthermore, we revealed a significant increase in coverage, at 80% identity, from < 20% (CSM) to > 75% (c-NCM). The algorithms, their applications and implications are discussed herein. 相似文献